Antifungal azoles trigger a xenobiotic detoxification pathway and chitin synthesis in Neurospora crassa

Abstract

The presence of antifungal drugs is prompting the fungal microorganisms to react by mechanisms broader than the resistance. The fungi evolved mechanisms, by which they respond to various stress conditions, including the presence of antifungal compounds. In this work, we studied the response of model filamentous fungus Neurospora crassa to azole antifungals in the broader context of the adaptation mechanisms. We demonstrated the increase in expression of filamentous fungi-specific genes encoding cytochrome enzymes of CYP65 clan and plasma membrane-localized ABCC transporters. Azoles appear not to conjugate with glutathione. Surprisingly, the azoles caused changes in the hyphae organization and the amount of chitin in cell wall by the same manner that was thought to be echinocandin-specific. The response to individual azoles appeared to be influenced by the structure of azole compound (prochloraz – main outlier). Taken together, these findings demonstrate the importance of study of stress response mechanisms, specifically in filamentous fungi. Many aspects of the reaction within azoles seem to be similar, though specificities are occurring.